Lysergic acid 2-butyl amide (2-Butyllysergamide, LSB) is an analogue of
LSD originally developed by Richard Pioch at
Eli Lilly in the 1950s,[2] but mostly publicised through research conducted by the team led by
David E. Nichols at
Purdue University. It is a
structural isomer of LSD, with the two ethyl groups on the amide nitrogen having been replaced by a single sec-butyl group, joined at the 2-position.[3] It is one of the few lysergamide derivatives to exceed the potency of LSD in animal drug discrimination assays, with the (R) isomer having an ED50 of 33nmol/kg for producing drug-appropriate responding, vs 48nmol/kg for LSD itself. The corresponding (R)-2-pentyl analogue has higher
binding affinity for the 5-HT1A and 5-HT2A receptors, but is less potent in producing drug-appropriate responding, suggesting that the butyl compound has a higher
efficacy at the receptor target.[4] The drug discrimination assay for LSD in rats involves both
5-HT1A and
5-HT2A mediated components, and while lysergic acid 2-butyl amide is more potent than LSD as a 5-HT1A agonist, it is slightly less potent as a 5-HT2A agonist, and so would probably be slightly less potent than LSD as a hallucinogen in humans. The main use for this drug has been in studies of the binding site at the 5-HT2Areceptor through which LSD exerts most of its pharmacological effects,[5] with the stereoselective activity of these unsymmetric monoalkyl lysergamides foreshadowing the subsequent development of compounds such as
lysergic acid 2,4-dimethylazetidide (LSZ).
^US patent 2997470, Richard P. Pioch, "LYSERGIC ACID AMIDES", published 1956-03-05, issued 1961-08-22
^Oberlender R, Pfaff RC, Johnson MP, Huang XM, Nichols DE (January 1992). "Stereoselective LSD-like activity in d-lysergic acid amides of (R)- and (S)-2-aminobutane". Journal of Medicinal Chemistry. 35 (2): 203–11.
doi:
10.1021/jm00080a001.
PMID1732537.
^Monte AP, Marona-Lewicka D, Kanthasamy A, Sanders-Bush E, Nichols DE (March 1995). "Stereoselective LSD-like activity in a series of d-lysergic acid amides of (R)- and (S)-2-aminoalkanes". Journal of Medicinal Chemistry. 38 (6): 958–66.
doi:
10.1021/jm00006a015.
PMID7699712.
^David E. Nichols. LSD and Its Lysergamide Cousins. The Heffter Review of Psychedelic Research. 2001;2:80-87.
Lysergic acid 2-butyl amide (2-Butyllysergamide, LSB) is an analogue of
LSD originally developed by Richard Pioch at
Eli Lilly in the 1950s,[2] but mostly publicised through research conducted by the team led by
David E. Nichols at
Purdue University. It is a
structural isomer of LSD, with the two ethyl groups on the amide nitrogen having been replaced by a single sec-butyl group, joined at the 2-position.[3] It is one of the few lysergamide derivatives to exceed the potency of LSD in animal drug discrimination assays, with the (R) isomer having an ED50 of 33nmol/kg for producing drug-appropriate responding, vs 48nmol/kg for LSD itself. The corresponding (R)-2-pentyl analogue has higher
binding affinity for the 5-HT1A and 5-HT2A receptors, but is less potent in producing drug-appropriate responding, suggesting that the butyl compound has a higher
efficacy at the receptor target.[4] The drug discrimination assay for LSD in rats involves both
5-HT1A and
5-HT2A mediated components, and while lysergic acid 2-butyl amide is more potent than LSD as a 5-HT1A agonist, it is slightly less potent as a 5-HT2A agonist, and so would probably be slightly less potent than LSD as a hallucinogen in humans. The main use for this drug has been in studies of the binding site at the 5-HT2Areceptor through which LSD exerts most of its pharmacological effects,[5] with the stereoselective activity of these unsymmetric monoalkyl lysergamides foreshadowing the subsequent development of compounds such as
lysergic acid 2,4-dimethylazetidide (LSZ).
^US patent 2997470, Richard P. Pioch, "LYSERGIC ACID AMIDES", published 1956-03-05, issued 1961-08-22
^Oberlender R, Pfaff RC, Johnson MP, Huang XM, Nichols DE (January 1992). "Stereoselective LSD-like activity in d-lysergic acid amides of (R)- and (S)-2-aminobutane". Journal of Medicinal Chemistry. 35 (2): 203–11.
doi:
10.1021/jm00080a001.
PMID1732537.
^Monte AP, Marona-Lewicka D, Kanthasamy A, Sanders-Bush E, Nichols DE (March 1995). "Stereoselective LSD-like activity in a series of d-lysergic acid amides of (R)- and (S)-2-aminoalkanes". Journal of Medicinal Chemistry. 38 (6): 958–66.
doi:
10.1021/jm00006a015.
PMID7699712.
^David E. Nichols. LSD and Its Lysergamide Cousins. The Heffter Review of Psychedelic Research. 2001;2:80-87.